Notice:

[Posted 07/09/2015]

AUDIENCE: Health Professional, Consumer

ISSUE: FDA is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on FDAs comprehensive review of new safety information, FDA is requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels. See the FDA Drug Safety Communication (Table 1) at: http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm for a list of non-aspirin nonsteroidal anti-inflammatory drug products.

Prescription NSAID labels will be revised to reflect the following information:

The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.

The risk appears greater at higher doses.

It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.

NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.

In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.

Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.

There is an increased risk of heart failure with NSAID use.

BACKGROUND: The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, FDA reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies, a large combined analysis of clinical trials, and other scientific publications. These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

RECOMMENDATION: Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

IMPORTANT WARNING:

People who take nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin, such as ketoprofen, may have a higher risk of having a heart attack or a stroke than people who do not take these medications. These events may happen without warning and may cause death. This risk may be higher for people who take NSAIDs for a long time. Tell your doctor if you or anyone in your family has or has ever had heart disease, a heart attack, or a stroke, if you smoke, and if you have or have ever had high cholesterol, high blood pressure, or diabetes. Get emergency medical help right away if you experience any of the following symptoms: chest pain, shortness of breath, weakness in one part or side of the body, or slurred speech.

If you will be undergoing a coronary artery bypass graft (CABG; a type of heart surgery), you should not take ketoprofen right before or right after the surgery.

NSAIDs such as ketoprofen may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may develop at any time during treatment, may happen without warning symptoms, and may cause death. The risk may be higher for people who take NSAIDs for a long time, are older in age, have poor health, or drink more than three alcoholic drinks per day while taking ketoprofen. Tell your doctor if you drink large amounts of alcohol or if you take any of the following medications: anticoagulants ('blood thinners') such as warfarin (Coumadin); aspirin; other NSAIDs such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn); or oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone). Also tell your doctor if you have or have ever had ulcers or bleeding in your stomach or intestines or other bleeding disorders. If you experience any of the following symptoms, stop taking ketoprofen and call your doctor: stomach pain, heartburn, vomit that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools.

Keep all appointments with your doctor and the laboratory. Your doctor will monitor your symptoms carefully and will probably order certain tests to check your body's response to ketoprofen. Be sure to tell your doctor how you are feeling so that your doctor can prescribe the right amount of medication to treat your condition with the lowest risk of serious side effects.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with prescription ketoprofen and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) to obtain the Medication Guide.

Why is this medication prescribed?

Prescription ketoprofen is used to relieve pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints). Prescription ketoprofen capsules are also used to relieve pain, including menstrual pain (pain that occurs before or during a menstrual period). Nonprescription ketoprofen is used to relieve minor aches and pain from headaches, menstrual periods, toothaches, the common cold, muscle aches, and backaches, and to reduce fever. Ketoprofen is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.

How should this medicine be used?

Prescription ketoprofen comes as a capsule and extended-release (long-acting) capsule to take by mouth. The capsules are usually taken three or four times a day for arthritis or every 6 to 8 hours as needed for pain. The extended-release capsules are usually taken once daily. If you take ketoprofen regularly, take it at around the same times every day.

Nonprescription ketoprofen comes as a tablet to take by mouth. It is usually taken with a full glass of water or other liquid every 4 to 6 hours as needed.

Follow the directions on the package or prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ketoprofen exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor or written on the label.

Ketoprofen may be taken with food or milk to prevent upset stomach. Your doctor may also recommend that you take ketoprofen with an antacid to reduce stomach upset.

Your doctor may start you on an average dose of prescription ketoprofen and may increase or decrease on your dose depending on how well you respond to the medication and the side effects you experience. Follow these directions carefully.

Stop taking nonprescription ketoprofen and call your doctor if your symptoms get worse, you develop new or unexpected symptoms, the part of your body that was painful becomes red or swollen, your pain lasts for more than 10 days or your fever lasts for more than 3 days.

Other uses for this medicine

Ketoprofen is also sometimes used to treat juvenile rheumatoid arthritis (a type of arthritis that affects children), ankylosing spondylitis (arthritis that mainly affects the spine), Reiter's syndrome (condition in which many parts of the body including the joints, eyes, genitals, bladder, and digestive system become swollen), shoulder pain caused by bursitis (inflammation of a fluid-filled sac in the shoulder joint) and tendinitis (inflammation of the tissue that connects muscle to bone), and gouty arthritis (attacks of joint pain caused by a build-up of certain substances in the joints). Talk to your doctor about the risks of using this medication for your condition.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before taking ketoprofen,

tell your doctor and pharmacist if you are allergic to ketoprofen, aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn), any other medications, or any of the inactive ingredients in ketoprofen capsules or extended release capsules. Ask your pharmacist for a list of the inactive ingredients.

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); diuretics ('water pills'); lithium (Eskalith, Lithobid); medications for diabetes; methotrexate (Rheumatrex); phenytoin (Dilantin); probenecid (Benemid); and sulfa antibiotics such as sulfisoxazole (Gantrisin) and sulfamethoxazole (in Bactrim, in Septra). Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.

tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or asthma, especially if you also have frequent stuffed or runny nose or nasal polyps (swelling of the lining of the nose); swelling of the hands, arms, feet, ankles, or lower legs; or liver or kidney disease.

tell your doctor if you are pregnant especially if you are in the last few months of your pregnancy, you plan to become pregnant, or you are breast-feeding. If you become pregnant while taking ketoprofen, call your doctor.

if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking ketoprofen.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can this medication cause?

Ketoprofen may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

constipation

diarrhea

sores in the mouth

headache

dizziness

nervousness

drowsiness

difficulty falling asleep or staying asleep

ringing in the ears

Some side effects may be serious. If you experience any of the following symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately. Do not take any more ketoprofen until you speak to your doctor.

Ketoprofen may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

lack of energy

drowsiness

nausea

vomiting

stomach pain

shallow breathing

seizures

coma

What other information should I know?

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking ketoprofen.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.